The cause of rheumatoid arthritis (RA) is currently unclear, but it has been speculated that the accumulation of fluid and subsequent damage to joints is the result of an autoimmune response. Activation of the cAMP dependent pathway has been shown to inhibit immune responses, and evidence also exists supporting a role for protein phosphorylation in this inhibition. The subcellular targeting and localization of protein kinases and phosphatases has emerged as an essential mechanism in the regulation of phosphorylation events. Therefore it is a goal of this proposal to study the role of subcellular targeting of the cAMP dependent protein kinase (PKA) in regulating immune response. The proposed studies will use methods and reagents currently used in Dr. Carr's laboratory and will specifically address 1) the importance of anchored PKA activity in mediating an immune response, and 2) the identification of PKA anchoring proteins in T lymphocytes.